Drug delivery device with retaining member

ABSTRACT

A drug delivery device is provided for delivering a drug to a target tissue site. The drug delivery device comprises a body comprising a proximal end and a distal end and a chamber disposed therebetween. An upper portion is disposed about the proximal end of the body. A retaining member is disposed within a wall of the body and engageable with the chamber and a plunger is configured for disposal within the upper portion and the chamber. The upper portion is movable about the proximal end of the body to open the chamber such that the plunger is disposed within a passageway defined within the chamber, and movement of the plunger in a distal direction pushes the retaining member such that the drug moves out of the body. Methods are also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional Application Ser.No. 61/892,357, filed on Oct. 17, 2013, titled “DRUG DELIVERY DEVICEWITH RETAINING MEMBER” and U.S. Provisional Application Ser. No.61/892,243, filed on Oct. 17, 2013, titled “DRUG DELIVERY DEVICE WITHRETAINING MEMBER,” the entire contents of which are incorporated hereinby reference into the present application.

BACKGROUND

Drugs may be delivered to patients by a variety of methods includingoral, intravenous, intramuscular, inhalation, topical, subcutaneousdelivery or delivery directly or locally to the treatment site (e.g.,intrathecally, intraspinally, intraarticularly, etc.). The method ofdelivery chosen depends, among other things, upon the condition beingtreated, desired therapeutic concentration of the drug to be achieved inthe patient and the duration of drug concentration that must bemaintained.

Recently, drug depots have been developed which allow a drug to beintroduced or administered to sites beneath the skin of a patient sothat the drug is slowly released over a long period of time. Such drugdepots allow the drug to be released from the depot in a relativelyuniform dose over weeks, months or even years. This method ofadministering drugs is becoming especially important and popular inmodulating the immune, inflammation and/or pain responses in treatmentof chronic conditions including rheumatoid arthritis, osteoarthritis,sciatica, carpal tunnel syndrome, lower back pain, lower extremity pain,upper extremity pain, cancer, tissue pain and pain associated withinjury or repair of cervical, thoracic, and/or lumbar vertebrae orintervertebral discs, rotator cuff, articular joint, TMJ, tendons,ligaments, muscles, and the like.

Previously, drug depots and other types of implants have been insertedinto the treatment site beneath the skin by use of a trocar device,which is a two-piece device that includes a cannula and an obdurator.The trocar device requires an incision to be made through the skin atthe site of implant of the drug depot using a separate instrument (e.g.,scalpel). A cannula and obdurator are inserted together through the skinat the incision site. Next, the obdurator is withdrawn, leaving thecannula in place as a guide for inserting the drug depot. The drug depotis inserted through the cannula, and the obdurator is used to push theimplant to the end of the cannula. The cannula and obdurator are thenwithdrawn completely, leaving the implant in place beneath the skin.

Typically, trocar devices are used to implant drug depots subcutaneouslyover a large area (e.g., 2-2.5 inches), with a typical drug depot in theorder of 1½ inches long. Thus, the trocar device is not suitable formany treatment sites because it lacks precision and may cause additionaltrauma to the tissue surrounding the site of implant.

Other drug depot devices have been developed to simplify implanting thedrug depots. These devices have a handle for one-handed implantation ofthe drug depot, a needle containing the drug depot to be implanted and arod positioned within the needle for pushing the drug depot out of theneedle. Once the needle containing the drug depot has been inserted atthe site of implant, a spring loaded trigger on the handle is activatedwhich causes the needle to be automatically withdrawn by a springleaving the implanted drug depot in place. Unfortunately, it is notpossible to control the motion of the needle in these devices becausethe needle will automatically retract upon activation of the trigger.The complex spring loaded propelling system and trigger of these devicesincrease the chances that the device will jam and fail to eject the drugdepot when required. Conventional needle and syringe devices have beenused to implant a drug depot to sites such as, for example, the epiduralspace. These devices typically utilize a syringe preloaded with the drugdepot and an epidural needle. The needle is inserted through the skin,supraspinus ligament, intraspinus ligament, ligamentum flavum and theninto the epidural space. The drug depot is delivered through the needleto the epidural space using the syringe plunger. Conventional needle andsyringe devices often do not easily allow controlled and precisionimplant of the drug depot. If multiple drug depot implants are needed,these conventional needle and syringe devices often do not allowaccurate placement of the implant in a manner so that one drug depotdoes not substantially interfere with the dissolution of the other.

New drug depot devices are needed, which can easily allow accurate andprecise implantation of a drug depot with minimal physical andpsychological trauma to a patient. When implanting several drug depots,a drug depot device is needed that accurately and precisely allowsplacement of the drug depot in a manner such that one depot does notsubstantially interfere with the dissolution of the others.

SUMMARY

New drug depot devices, which can easily allow accurate and preciseimplantation of a drug depot with minimal physical and psychologicaltrauma to a patient are provided. One advantage of the drug depot deviceis that it allows the user to dispense multiple doses of the drug insequence.

In various embodiments, a drug depot device is provided for delivering adrug to a target tissue site, the drug depot device comprising a bodycomprising a proximal end and a distal end and a chamber disposedtherebetween. An upper portion is disposed about the proximal end of thebody. A retaining member is disposed within a wall of the body and isengageable with the chamber, and a plunger is configured for disposalwithin the upper portion and the chamber. The upper portion is movableabout the proximal end of the body to open the chamber such that theplunger is disposed within a passageway defined within the chamber, andmovement of the plunger in a distal direction pushes the retainingmember such that the drug moves out of the body.

In one embodiment, a drug delivery device is provided for delivering adrug to a target tissue site, the drug delivery device comprising a bodycomprising a proximal end and a distal end and a chamber comprising apassageway disposed therebetween. An external surface comprises a firstguide and a second guide. A retaining member is disposed within a walldefined by the external surface of the body and is engageable with thechamber. An internal plunger comprises a handle and the plunger isconfigured for disposal within the body. The plunger handle isconfigured for slidable engagement with the first guide and the secondguide and movement of the plunger handle moves the plunger through thepassageway of the body and engages with the retaining member such thatthe drug is dispensed from the delivery device.

In another embodiment, a method of delivering a drug to a target tissuesite is provided, the method comprising: introducing a drug deliverydevice comprising a body comprising a proximal end and a distal end anda chamber comprising a passageway disposed therebetween, an upperportion disposed about the proximal end of the body that rotates aboutthe proximal end of the body to open the chamber, and a retaining memberdisposed within a wall of the body and engageable with the chamber;attaching a needle with the distal end of the body; inserting a plungerinto the passageway, and moving the plunger in a first position to pushthe retaining member outward and moving the plunger in a second positionsuch that the drug moves through the needle and is ejected from thedelivery device and into the target tissue site.

Additional features and advantages of various embodiments will be setforth in part in the description that follows, and in part will beapparent from the description, or may be learned by practice of variousembodiments. The objectives and other advantages of various embodimentswill be realized and attained by means of the elements and combinationsparticularly pointed out in the description and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying drawings where:

FIGS. 1-3 illustrate front views of one embodiment of a drug deliverydevice. The drug delivery device comprises a body comprising a proximalend and a distal end and a chamber disposed therebetween; an upperportion disposed about the proximal end of the body; a retaining memberdisposed within a wall of the body and engageable with the chamber; anda plunger configured for disposal within the upper portion and thechamber. A needle is attached to the distal end of the body. The upperportion is movable about the proximal end of the body to open thechamber such that the plunger is disposed within a passageway definedwithin the chamber, and movement of the plunger in a distal directionpushes the retaining member outward such that the drug moves through theneedle and is ejected from the delivery device and into the targettissue site.

FIGS. 4-6 illustrate cross-sectional views of the embodiment of the drugdelivery device shown in FIGS. 1-3. In some embodiments, the upperportion comprises an internally threaded collet and a first tab and asecond tab. The collet rotates about a threaded portion at the proximalend of the body and the chamber comprises a third tab and a fourth tabconfigured for engagement with the first tab and the second tab.

FIGS. 7-8 illustrate front views of the embodiment of the drug deliverydevice as shown in FIGS. 1-3. In some embodiments, the wall of the bodycomprises an opening configured for visual inspection of the drug.

FIG. 9 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 1-3. A and Billustrate the needle being attached to the body of the device. C and Dillustrate the upper portion being rotated. E illustrates the devicebeing positioned over the target tissue site. F and G illustrate theplunger being inserted into the body of the device. The plunger is movedin a downward direction and the drug (e.g., pellets) is then ejected outof the device. H illustrates the entire assembly being removed from thetarget tissue site.

FIGS. 10-12 illustrate front views of an embodiment of the drug deliverydevice. The drug delivery device comprises a body comprising a proximalend and a distal end and a chamber is disposed therebetween comprising apassageway. A retaining member is disposed within a wall of the body andis engageable with the chamber. A needle is attached to the distal endof the body. The device comprises a plunger that is configured forinsertion at the proximal end of the device and is configured fordisposal within the body of the device. Movement of the plunger in adistal direction pushes the retaining member outward such that the drugmoves through the needle and is ejected from the delivery device andinto the target tissue site.

FIGS. 13-16 illustrate front and side views respectively of theembodiment of the drug delivery device as shown in FIGS. 10-12. In someembodiments, the retaining member is transparent and comprises a windowconfigured for visual inspection of the drug. In some embodiments, theretaining member engages with the wall of the body via snap fitengagement with press fit posts, adhesive, solvent welded, heat welded,spring loaded or magnetic engagement.

FIG. 17 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 10-12. A and Billustrate the needle being attached to the body of the device. Cillustrates the device being positioned over the target tissue site. D-Fillustrates the plunger being inserted into the body of the device. Theplunger is moved in a downward direction and the drug (e.g., pellets) isthen ejected out of the device. The entire assembly fits completely intothe body of the drug delivery device. G illustrates the entire assemblybeing removed from the target tissue site.

FIGS. 18-28 illustrate front and side views of an embodiment of the drugdelivery device. The drug delivery device comprises a body comprising aproximal end and a distal end and a chamber comprising a passagewaydisposed therebetween. An external surface comprises a first guide and asecond guide. A retaining member is disposed within a wall defined bythe external surface of the body and is engageable with the chamber. Aneedle is configured for engagement with the distal end of the body.Drug delivery device comprises an internal plunger comprising a handle,and is configured for disposal within the body. The plunger handle isconfigured for slidable engagement with the first guide and the secondguide and movement of the plunger handle moves the plunger through thepassageway of the body and engages with the retaining member such thatthe drug moves through the needle and is ejected from the deliverydevice and into the target tissue site. In some embodiments, theretaining member comprises a first channel and a second channel. Invarious embodiments, the retaining member is rotatable relative to thebody and is transparent and comprises a window configured for visualinspection of the drug. In some embodiments, the body comprises a wingtransverse to the distal end of the body. In some embodiments, theretaining member is rotated in a direction such that the plunger isinserted into the first channel during movement of the handle in adistal direction. In various embodiments, the handle is disposed aboutthe external surface of the body and engages the first guide and thesecond guide via a first inner protuberance and a second innerprotuberance.

FIG. 29 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 18-28. A and Billustrate the needle being attached to the body of the device. Cillustrates the device being positioned over the target tissue site. Dand E illustrate the plunger being retracted to the proximal end of thedevice. F illustrates that the retaining member is then rotated intoplace. G illustrates the handle of the plunger being gripped and movedin a downward direction, and the drug (e.g., pellets) is then ejectedout of the device. H illustrates the drug delivery device being removedfrom the target tissue site.

FIGS. 30-36 illustrate side and detailed views of an embodiment of thedrug delivery device. The drug delivery device comprises a bodycomprising a proximal end and a distal end and a chamber comprising apassageway disposed therebetween. An external surface comprises a firstguide and a second guide. A retaining member is disposed within a walldefined by the external surface of the body and is engageable with thechamber. A needle is configured for engagement with the distal end ofthe body. Drug delivery device comprises an internal plunger comprisinga handle, and is configured for disposal within the body. The plungerhandle is configured for slidable engagement with the first guide andthe second guide and movement of the plunger handle moves the plungerthrough the passageway of the body and engages with the retaining membersuch that the drug moves through the needle and is ejected from thedelivery device and into the target tissue site. In some embodiments,the retaining member comprises a first channel and a second channel. Invarious embodiments, the retaining member is rotatable relative to thebody and is transparent and comprises a window configured for visualinspection of the drug. In some embodiments, the body comprises a wingtransverse to the distal end of the body. In some embodiments, theretaining member is rotated in a direction such that the plunger isinserted into the first channel during movement of the handle in adistal direction. In some embodiments, the handle comprises a first partand a second part and the first part is configured for disposal withinthe first guide and the second part is configured for disposal withinthe second guide.

FIG. 37 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 30-36. A and Billustrate a needle being attached to the body of the device. Cillustrates the device being positioned over the target tissue site. Theplunger is retracted to the proximal end of the device. D illustratesthe retaining member being rotated into place. E illustrates the handleof the plunger being gripped and moved in a downward direction, and thedrug (e.g., pellets) is then ejected out of the device. F illustratesthe drug delivery device being removed from the target tissue site.

FIGS. 38-44 illustrate an embodiment of the drug delivery device. Thedrug delivery device comprises a body comprising a proximal end and adistal end and a chamber comprising a passageway disposed therebetween.An external surface comprises a first guide and a second guide. Aretaining member is disposed within a wall defined by the externalsurface of the body and is engageable with the chamber. A needle isconfigured for engagement with the distal end of the body. Drug deliverydevice comprises an internal plunger comprising a handle, and isconfigured for disposal within the body. The plunger handle isconfigured for slidable engagement with the first guide and the secondguide and movement of the plunger handle moves the plunger through thepassageway of the body and engages with the retaining member such thatthe drug moves through the needle and is ejected from the deliverydevice and into the target tissue site. In some embodiments, theretaining member comprises a first channel and a second channel. In someembodiments, the handle is disposed about the external surface of thebody and engages the first guide and the second guide via a first innerprotuberance and a second inner protuberance and the handle engages atleast a first indent defined by the external surface of the body via athird inner protuberance. In some embodiments, the handle is moved aboutthe body when squeezed. In various embodiments, the retaining member istransparent and comprises a window configured for visual inspection ofthe drug. In some embodiments, the retaining member is pushed in aninward direction such that the plunger is inserted into the firstchannel during movement of the handle in a distal direction to deliverthe drug to the needle.

FIG. 45 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 38-44. A and Billustrate a needle being attached to the body of the device. Cillustrates the device being positioned over the target tissue site. Dand E illustrate the plunger handle being squeezed and retracted to theproximal end of the device. F illustrates the retaining member beingpushed in an inward direction and being flush with the body. Gillustrates the handle of the plunger being slided and moved in adownward direction, and the drug (e.g., pellets) is then ejected out ofthe device. H illustrates the drug delivery device being removed fromthe target tissue site.

It is to be understood that the figures are not drawn to scale. Further,the relation between objects in a figure may not be to scale, and may infact have a reverse relationship as to size. The figures are intended tobring understanding and clarity to the structure of each object shown,and thus, some features may be exaggerated in order to illustrate aspecific feature of a structure.

DETAILED DESCRIPTION

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present invention. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques.

Notwithstanding that the numerical ranges and parameters setting forth,the broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, e.g., 5.5 to 10.

It is noted that, as used in this specification and the appended claims,the singular forms “a,” “an,” and “the,” include plural referents unlessexpressly and unequivocally limited to one referent. Thus, for example,reference to “a drug depot” includes one, two, three or more drugdepots.

Reference will now be made in detail to certain embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. While the invention will be described in conjunction with theillustrated embodiments, it will be understood that they are notintended to limit the invention to those embodiments. On the contrary,the invention is intended to cover all alternatives, modifications, andequivalents, which may be included within the invention as defined bythe appended claims.

The headings below are not meant to limit the disclosure in any way;embodiments under any one heading may be used in conjunction withembodiments under any other heading.

New drug depot devices, which can easily allow the accurate and preciseimplantation of multiple drug depots with minimal physical andpsychological trauma to a patient are provided. In various embodimentsthe drug depot device allows the user to dispense multiple drug depots,in sequence, to a site beneath the skin of the patient. In variousembodiments, when several drug depots are to be implanted, a drug depotdevice is provided that accurately allows placement of the drug depot ina manner such that one depot does not substantially interfere with thedissolution of the others.

In some embodiments, the drug delivery device contains and protects thedrug (e.g., drug pellets) and ensures that the drug cannot be deployedaccidentally, minimizing the number of work flow steps for the injectionprocedure and allowing for visual inspection of the drug.

FIGS. 1-8 illustrate one embodiment of a drug delivery device 50. Thedrug delivery device comprises a body 52 comprising a proximal end 54and a distal end 56. Longitudinal axis A extends between the proximalend and the distal end. A chamber 58 is disposed between the proximalend and the distal end. An upper portion 60 is disposed about theproximal end of the body. A retaining member 62 is slidably disposedwithin a transverse channel 61 defined by a wall of the body, and theretaining member is engageable with the chamber. The retaining member isconfigured to prevent a drug 68 (e.g., drug depot) from deployingaccidentally from the drug delivery device by creating a movable barrierwhich closes off a passageway 67 defined within the chamber, where thedrug may be stored. In some embodiments, the retaining member isvariously shaped. In some embodiments, the retaining member iscylindrical, rectangular, pin shaped and/or screw shaped. In variousembodiments, the retaining member comprises a distal end 63 configuredfor engagement with the drug (e.g., drug depot). In some embodiments,the end is variously configured, such as, angled, arcuate, tapered,flat, irregular, and/or grooved. The retaining member is manually pushedinward, thereby moving across the entire horizontal distance of thepassageway, closing off the passageway and preventing the drug (e.g.,drug depot) from deploying from the drug delivery device. The end of theretaining member will engage with the drug (e.g., drug depot) such thatthe drug remains above the end of the retaining member. In someembodiments, the retaining member is transverse relative to the body. Insome embodiments, the retaining member can be monolithic with the bodyand is activated when the plunger and/or the drug depot contacts it orit can be a separate piece attached to the body.

A plunger 64 is configured for longitudinal disposal within the upperportion and the chamber. A needle 66 is attached to the distal end ofthe body. In some embodiments, the needle is detachable from the body ofthe device. The upper portion is rotatable about the proximal end of thebody to open the chamber such that the plunger is disposed within thepassageway, and movement of the plunger in a distal direction pushes theretaining member outward such that the drug (e.g., drug depot) movesthrough the needle and is ejected from the delivery device and into thetarget tissue site. In various embodiments, the plunger engages the drugand not the needle. In some embodiments, the plunger stops adjacent theneedle and the drug ejects from the device via gravity. In someembodiments, the plunger moves through the passageway and passes throughthe needle to assist in dispensing and ejecting the drug.

In some embodiments, the upper portion comprises an internally threadedcollet 70 and comprises a first tab 72 and a second tab 74. The colletrotates about a threaded portion 76 at the proximal end of the body andthe chamber comprises a third tab 78 and a fourth tab 80 configured forengagement with the first tab and the second tab. The first and thesecond tab are configured to guide the drug (e.g., drug depot) throughthe body using the plunger. In some embodiments, the collet can beattached to the body by other means, such as for example, a rod, pin,screw, clip, etc.

In some embodiments, the body comprises an external first flange 82 andan external second flange 84. In various embodiments, the collet isrotated in a direction, aligning the external first flange and theexternal second flange together such that the passageway is opened andthe plunger is disposed within the passageway. In various embodiments,the first flange indicates alignment of the delivery device with theneedle. In some embodiments, rotation of the collet is consistent withrotation to attach the needle to the body. In various embodiments, theplunger comprises a handle 86 configured to snap into the proximal endof the body. In some embodiments, the wall of the body comprises anopening 88 configured for visual inspection of the drug. In someembodiments, the drug depot can be physically inspected by inserting arod 89 or pin into the opening.

FIG. 9 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 1-8. Theneedle is attached to the body of the device and the upper portion isrotated. The plunger is inserted into the body of the device. Theplunger is moved in a downward direction into and through thepassageway. As the plunger moves, it contacts the retaining member,moving the retaining member in an outward direction to open thepassageway. The plunger contacts the drug (e.g., pellets), and the drugis ejected out of the device. The entire assembly is then removed fromthe target tissue site.

FIGS. 10-12 illustrate one embodiment of the drug delivery device 150.The drug delivery device comprises a body 152 comprising a proximal end154 and a distal end 156 and a chamber 158 disposed therebetweencomprising a passageway 167. A longitudinal axis B extends between theproximal end and the distal end. A retaining member 162 is disposedwithin a wall of the body and engageable with the chamber. The retainingmember is configured to prevent the drug (e.g., drug depot) fromdeploying accidentally from the drug delivery device by creating amovable barrier which closes off the passageway, where the drug may bestored. The device comprises a plunger 164 that is configured forlongitudinal insertion at the proximal end of the device and isconfigured for disposal within the body of the device. A needle 166 isattached to the distal end of the body. Movement of the plunger in adistal direction pushes the retaining member outward such that the drugmoves through the needle and is ejected from the delivery device andinto the target tissue site. In various embodiments, the plunger engagesthe drug and not the needle. In some embodiments, the plunger stopsadjacent the needle and the drug ejects from the device via gravity. Insome embodiments, the plunger moves through the passageway and passesthrough the needle to assist in dispensing and ejecting the drug.

In some embodiments, the retaining member is transparent and comprises awindow 163 configured for visual inspection of the drug. In someembodiments, the retaining member engages with the wall of the body viasnap fit engagement with press fit posts, adhesive, solvent welded, heatwelded, spring loaded or magnetic engagement. In various embodiments,the retaining member is variously shaped. In some embodiments, theretaining member is cylindrical, rectangular, pin shaped and/or screwshaped. In some embodiments, the retaining member is transverse relativeto the body.

FIG. 17 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 10-12. Aneedle is attached to the body of the drug delivery device. A plunger isinserted into the body of the drug delivery device. The plunger is movedin a downward direction into and through the passageway. As the plungermoves, it contacts the retaining member, moving the retaining member inan outward direction to open the passageway. The plunger contacts thedrug (e.g., pellets), and the drug is ejected out of the device. Theentire assembly fits completely into the body of the drug deliverydevice. The drug delivery device is then removed from the target tissuesite.

FIGS. 18-28 illustrate an embodiment of the drug delivery device 250.The drug delivery device comprises a body 252 comprising a proximal end254 and a distal end 256 and a chamber 258 comprising a passageway 267disposed therebetween. A longitudinal axis C extends between theproximal end and the distal end. An external surface 265 comprises afirst guide 269 and a second guide 271. A retaining member 262 isdisposed within a wall defined by the external surface of the body andis engageable with the chamber. The retaining member is configured toprevent the drug (e.g., drug depot) from deploying accidentally from thedrug delivery device. In various embodiments, the retaining member isvariously shaped. In some embodiments, the retaining member iscylindrical, rectangular, pin shaped and/or screw shaped. In someembodiments, the retaining member comprises an external tab 255configured to facilitate rotatable movement of the retaining member. Insome embodiments, the retaining member is transverse relative to thebody.

A needle 266 is configured for engagement with the distal end of thebody. Drug delivery device comprises an internal plunger 264 comprisinga handle 286, and is configured for longitudinal disposal within thebody. The plunger handle is configured for slidable engagement with thefirst guide and the second guide and movement of the plunger handlemoves the plunger through the passageway of the body and engages withthe retaining member such that the drug moves through the needle and isejected from the delivery device and into the target tissue site. Invarious embodiments, the plunger engages the drug and not the needle. Insome embodiments, the plunger stops adjacent the needle and the drugejects from the device via gravity. In some embodiments, the plungermoves through the passageway and passes through the needle to assist indispensing and ejecting the drug.

In some embodiments, the retaining member comprises a first channel 273and a second channel 275. At least one of the channels is configured fordisposal of the drug (e.g., drug depot). In various embodiments, theretaining member is rotatable relative to the body and is transparentand comprises a window 263 configured for visual inspection of the drug.In various embodiments, the body comprises a wing 277 transverse to thedistal end of the body. In some embodiments, the wing is a grip portionwhich assists in the handling of the drug delivery device during use. Insome embodiments, the retaining member is rotated in a direction suchthat the plunger is inserted into the first channel during movement ofthe handle in a distal direction. In various embodiments, the handle isdisposed about the external surface of the body and engages the firstguide and the second guide via a first inner protuberance 279 and asecond inner protuberance 281.

FIG. 29 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 18-28. Aneedle is attached to the body of the drug delivery device. The plungeris retracted to the proximal end of the device. The retaining member isthen rotated into place. The handle of the plunger is then gripped andmoved in a downward direction, moving the plunger into and through thepassageway, and into the channel where the drug (e.g., pellets) isdisposed. The drug is pushed and ejected out of the device via downwardmovement of the plunger through the channel. The drug delivery device isthen removed from the target tissue site.

FIGS. 30-36 illustrate an embodiment of the drug delivery device 350.The drug delivery device comprises a body 352 comprising a proximal end354 and a distal end 356 and a chamber 358 comprising a passageway 367disposed therebetween. A longitudinal axis D extends between theproximal end and the distal end. An external surface 365 comprises afirst guide 367 and a second guide 369. A retaining member 362 isdisposed within a wall defined by the external surface of the body andis engageable with the chamber. The retaining member is configured toprevent the drug (e.g., drug depot) from deploying accidentally from thedrug delivery device. In various embodiments, the retaining member isvariously shaped. In some embodiments, the retaining member iscylindrical, rectangular, pin shaped and/or screw shaped. In someembodiments, the retaining member comprises an external tab 355configured to facilitate rotatable movement of the retaining member. Insome embodiments, the retaining member is transverse relative to thebody.

A needle 366 is configured for engagement with the distal end of thebody. Drug delivery device comprises an integrated internal plunger 364comprising a handle 386, and is configured for longitudinal disposalwithin the body. The plunger handle is configured for slidableengagement with the first guide and the second guide and movement of theplunger handle moves the plunger through the passageway of the body andengages with the retaining member such that the drug moves through theneedle and is ejected from the delivery device and into the targettissue site. In various embodiments, the plunger engages the drug andnot the needle. In some embodiments, the plunger stops adjacent theneedle and the drug ejects from the device via gravity. In someembodiments, the plunger moves through the passageway and passes throughthe needle to assist in dispensing and ejecting the drug.

In some embodiments, the retaining member comprises a first channel 373and a second channel 375. At least one of the channels is configured fordisposal of the drug (e.g., pellets). In various embodiments, theretaining member is rotatable relative to the body and is transparentand comprises a window 363 configured for visual inspection of the drug.In various embodiments, the body comprises a wing 377 transverse to thedistal end of the body. In some embodiments, the wing is a grip portionwhich assists in the handling of the drug delivery device during use. Insome embodiments, the retaining member is rotated in a direction suchthat the plunger is inserted into the first channel during movement ofthe handle in a distal direction. In some embodiments, the handlecomprises a first part 383 and a second part 385 and the first part isconfigured for disposal within the first guide and the second part isconfigured for disposal within the second guide.

FIG. 37 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 30-36. Aneedle is attached to the body of the drug delivery device. The plungeris retracted to the proximal end of the device. The retaining member isthen rotated into place via the tab. The handle of the plunger is thengripped and moved in a downward direction into and through thepassageway, and into the channel where the drug (e.g., pellets) isdisposed. The drug is pushed and ejected out of the device via downwardmovement of the plunger through the channel. The drug delivery device isthen removed from the target tissue site.

FIGS. 38-44 illustrate an embodiment of the drug delivery device 450.The drug delivery device comprises a body 452 comprising a proximal end454 and a distal end 456 and a chamber 458 comprising a passageway 467disposed therebetween. A longitudinal axis E extends between theproximal end and the distal end. An external surface 465 comprises afirst guide 467 and a second guide 469. A retaining member 462 isdisposed within a wall defined by the external surface of the body andis engageable with the chamber. The retaining member is configured toprevent the drug (e.g., drug depot) from deploying accidentally from thedrug delivery device. In various embodiments, the retaining member isvariously shaped. In some embodiments, the retaining member iscylindrical, rectangular, pin shaped and/or screw shaped. In someembodiments, the retaining member is transverse relative to the body.

A needle 466 is configured for engagement with the distal end of thebody. Drug delivery device comprises an integrated internal plunger 464comprising a handle 486, and configured for longitudinal disposal withinthe body. The plunger handle is configured for slidable engagement withthe first guide and the second guide and movement of the plunger handlemoves the plunger through the passageway of the body and engages withthe retaining member such that the drug moves through the needle and isejected from the delivery device and into the target tissue site. Invarious embodiments, the plunger engages the drug and not the needle. Insome embodiments, the plunger stops adjacent the needle and the drugejects from the device via gravity. In some embodiments, the plungermoves through the passageway and passes through the needle to assist indispensing and ejecting the drug.

In some embodiments, the retaining member comprises a first channel 473and a second channel 475. At least one of the channels is configured fordisposal of the drug (e.g., pellets). In some embodiments, the handle isdisposed about the external surface of the body and engages the firstguide and the second guide via a first inner protuberance 479 and asecond inner protuberance 481 and the handle engages at least a firstindent 487 defined by the external surface of the body via a third inner489 protuberance. In some embodiments, the handle is moved about thebody when squeezed. In various embodiments, the retaining member istransparent and comprises a window 463 configured for visual inspectionof the drug. In some embodiments, the retaining member is pushed in aninward direction such that the plunger is inserted into the firstchannel during movement of the handle in a distal direction to deliverthe drug to the needle.

FIG. 45 illustrates a method of delivery of a drug to a target tissuesite utilizing the drug delivery device as shown in FIGS. 38-44. Aneedle is attached to the body of the drug delivery device. The plungerhandle is squeezed and retracted to the proximal end of the device. Theretaining member is then pushed in an inward direction and is flush withthe body. The handle of the plunger is then slided and moved in adownward direction into and through the passageway, and into the channelwhere the drug (e.g., pellets) is disposed. The drug is pushed andejected out of the device via downward movement of the plunger throughthe channel. The drug delivery device is then removed from the targettissue site.

Cannula or Needle

The cannula or needle of the drug depot device is designed to causeminimal physical and psychological trauma to the patient. Cannulas orneedles include tubes that may be made from materials, such as forexample, polyurethane, polyurea, polyether(amide), PEBA, thermoplasticelastomeric olefin, copolyester, and styrenic thermoplastic elastomer,steel, aluminum, stainless steel, nitinol, titanium, metal alloys withhigh non-ferrous metal content and a low relative proportion of iron,carbon fiber, glass fiber, plastics, ceramics or combinations thereof.The cannula or needle may optionally include one or more taperedregions. In various embodiments, the cannula or needle may be beveled.The cannula or needle may also have a tip style vital for accuratetreatment of the patient depending on the site for implantation.Examples of tip styles include, for example, Trephine, Cournand, Veress,Huber, Seldinger, Chiba, Francine, Bias, Crawford, deflected tips,Hustead, Lancet, or Tuohey. In various embodiments, the cannula orneedle may also be non-coring and have a sheath covering it to avoidunwanted needle sticks.

The cannula or needle of the drug depot device has a diameter that islarger than the diameter of at least part of the plunger (e.g., tip,middle, etc.) to allow at least part of the plunger to be slidablyreceived within the cannula or needle. In various embodiments, thediameter of the cannula or needle is substantially the same throughout.In other embodiments, the diameter of the needle or cannula becomessmaller approaching the distal end for drug delivery.

The dimensions of the hollow cannula or needle, among other things, willdepend on the site for implantation. For example, the width of theepidural space is only about 3-5 mm for the thoracic region and about5-7 mm for the lumbar region. Thus, the needle or cannula, in variousembodiments, can be designed for these specific areas. Some examples oflengths of the cannula or needle may include, but are not limited to,from about 50 to 150 mm in length, for example, about 65 mm for epiduralpediatric use, about 85 mm for a standard adult and about 150 mm for anobese adult patient. In some embodiments, the length of the cannula isabout 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149 or 150 mm. The thickness of thecannula or needle will also depend on the site of implantation. Invarious embodiments, the thickness includes, but is not limited to, fromabout 0.05 to about 1.655 mm. In some embodiments, the thickness of thecannula or needle is about 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35,0.40, 0.45, 0.50, 0.55, 0.60, 0.65, 0.70, 0.75, 0.80, 0.85, 0.90, 0.95,1.0, 1.05, 1.10, 1.15, 1.20, 1.25, 1.30, 1.35, 1.40, 1.45, 1.50, 1.55,1.60, 1.65 or 1.655 mm. The gauge of the cannula or needle may be thewidest or smallest diameter or a diameter in between for insertion intoa human or animal body. The widest diameter is typically about 14 gauge,while the smallest diameter is about 25 gauge. In various embodiments,the gauge of the needle or cannula is about 17 to about 25 gauge. Insome embodiments, the gauge of the needle or cannula is about 17, 18,19, 20, 21, 22, 23, 24 or about 25 gauge.

In various embodiments, the plunger, cannula or drug depot includemarkings that indicate location at or near the site beneath the skin.Radiographic markers can be included on the drug depot to permit theuser to accurately position the depot into the site of the patient.These radiographic markers will also permit the user to track movementand degradation of the depot at the site over time. In this embodiment,the user may accurately position the depot in the site using any of thenumerous diagnostic-imaging procedures. Such diagnostic imagingprocedures include, for example, X-ray imaging or fluoroscopy. Examplesof such radiographic markers include, but are not limited to, barium,calcium phosphate, and/or metal beads.

In various embodiments, the needle or cannula may include a transparentor translucent portion that can be visualizable by ultrasound,fluoroscopy, x-ray, or other imaging techniques. In such embodiments,the transparent or translucent portion may include a radiopaque materialor ultrasound responsive topography that increases the contrast of theneedle or cannula relative to the absence of the material or topography.

In various embodiments, the drug depot comprises a drug cartridgecontaining drug pellets loaded within the chamber of the drug cartridge,when the plunger is moved to the extended position, the drug cartridgewill remain within the housing and the chamber of the drug cartridgewill guide the tip of the plunger longitudinally and the drug pelletwill be released from it when it is in the extended position. Asubsequent or second pellet may be administered by repositioning theneedle at a target site, removing the plunger so that it is at aposition above the drug cartridge, and rotating the drug cartridge at aposition horizontal to the plunger and cannula to align the drug chamberand drug depot with the cannula and plunger. The plunger is then slid ina vertical direction within the housing to release the drug depot fromthe chamber into the cannula where the drug depot can be delivered tothe target site by pushing it out the tip of the needle using theplunger. In this way, sequential delivery of a drug can be accomplished.Thus, the above procedure (e.g., repositioning the needle, removing theplunger, rotating the drug cartridge, inserting the plunger, deliveringthe drug depot) can be repeated multiple times to deliver multiple drugdepots to the target tissue site.

In various embodiments, surrounding the opening of the proximal end ofthe cannula or needle is a generally cylindrical hub having anengagement means (shown as internal threading) for engaging the housing.Engagement means include, but are not limited to, threading, tracks,clips, ribs, projections, and the like that allow a secure connectionbetween the housing and the proximal end of the cannula. For example, invarious embodiments the engagement means may be a luer lock connection,where the cannula has mating threads that mate with the threads disposedon or in the housing.

Body

The body may be of various shapes including, but not limited to,cylindrical or round such that the body allows for the affixation to thecannula as well as the drug cartridge and the plunger.

The body may comprise a variety of materials, such as, for example,polyurethane, polyurea, polyether(amide), PEBA, thermoplasticelastomeric olefin, copolyester, and styrenic thermoplastic elastomer,steel, nitinol, aluminum, stainless steel, titanium, metal alloys withhigh non-ferrous metal content and a low relative proportion of iron,carbon fiber, glass fiber, plastics, ceramics or combinations thereof.

Like the cannula or needle, in various embodiments, the body may havedose indicator markings (e.g., numbers, lines, letters, radiographicmarkers, etc.) to indicate the number of drug depots delivered. Invarious embodiments, the plunger includes markings that indicatelocation at or near the site beneath the skin.

The body may have contours and allow easy grasping of the device duringuse for insertion of the drug depot. The body can be angled for rightand left hand users or can be generic for both hands. In variousembodiments, the body can comprise an upper opening, a middle opening,and a lower opening. The upper, middle and lower openings allow aplunger to slide through the openings.

Plunger

Although the first end of the plunger is shown as a knob, it will beunderstood that the knob can be a top, dial, cap, handle or any memberthat allows the user to utilize the plunger. The plunger has a secondend that includes a tip, which is capable of moving the drug depotwithin the cannula. In other embodiments, the tip of the plunger issufficiently pointed so that it is capable of insertion to the sitebeneath the skin of the patient and the cannula or needle is blunted andused to guide the drug depot to the site. In some embodiments, theplunger is external or outside of the body. In some embodiments, theplunger is an integrated internal plunger longitudinally disposed withinthe body.

The plunger has a diameter less than the cannula or needle so that itcan be slidably received therein. The plunger may be longer, the samesize, or smaller in length than the cannula or needle. In embodimentswhere the plunger extends from the distal end of the cannula or needle,the plunger is usually longer than the cannula or needle. In someembodiments, the tip of the plunger can be sharp or blunt. The sharpertip of the plunger can be used in embodiments where the drug cartridgehas superior and inferior covers that the sharp tip of the plunger canpierce.

The plunger may be made from materials, such as for example,polyurethane, polyurea, polyether(amide), PEBA, thermoplasticelastomeric olefin, copolyester, and styrenic thermoplastic elastomer,steel, aluminum, stainless steel, titanium, nitinol, metal alloys withhigh non-ferrous metal content and a low relative proportion of iron,carbon fiber, glass fiber, plastics, ceramics or combinations thereof.The plunger may optionally include one or more tapered regions.

Like the cannula or needle, in various embodiments, the plunger may havedose indicator markings (e.g., numbers, lines, letters, radiographicmarkers, etc.) to indicate the number of drug depots delivered. Invarious embodiments, the plunger includes markings that indicatelocation at or near the site beneath the skin.

The plunger tip, which may be a complementary shape to the drug pellet,allows the plunger tip to snuggly fit within the end of the drug pelletfor easier drug delivery. The drug pellet may have a rounded end foreasier insertion at the desired site.

Drug Depot

In various embodiments, the device comprises a drug depot. A drug depotcomprises a physical structure to facilitate implantation and retentionin a desired site (e.g., a synovial joint, a disc space, a spinal canal,a tissue of the patient, etc.). The drug depot also comprises the drug.The term “drug” as used herein is generally meant to refer to anysubstance that alters the physiology of the patient. The term “drug” maybe used interchangeably herein with the terms “therapeutic agent”,“therapeutically effective amount”, and “active pharmaceuticalingredient”. It will be understood that a “drug” formulation may includemore than one therapeutic agent, wherein exemplary combinations oftherapeutic agents include a combination of two or more drugs. The drugprovides a concentration gradient of the therapeutic agent for deliveryto the site. In various embodiments, the drug depot provides an optimaldrug concentration gradient of the therapeutic agent at a distance of upto about 1 mm to about 5 cm from the implant site.

Examples of drugs suitable for use in the drug depot, include, but arenot limited to an anti-inflammatory agent, analgesic agent, orosteoinductive growth factor or a combination thereof. Anti-inflammatoryagents include, but are not limited to, salicylates, diflunisal,indomethacin, ibuprofen, naproxen, tolmetin, ketorolac, diclofenac,ketoprofen, fenamates (mefenamic acid, meclofenamic acid), enolic acids(piroxicam, meloxicam), nabumetone, celecoxib, etodolac, nimesulide,apazone, gold, sulindac or tepoxalin; antioxidants, such asdithiocarbamate, and other compounds such assulfasalazine[2-hydroxy-5-[-4-[C2-pyridinylamino)sulfonyl]azo]benzoicacid], steroids, such as fluocinolone, cortisol, cortisone,hydrocortisone, fludrocortisone, prednisone, prednisolone,methylprednisolone, triamcinolone, betamethasone, dexamethasone,beclomethasone, fluticasone, protein inhibitors of TNF, such asetanercept, Remicade, IL-1, such as Kineret®, p 38, RANK, RANKL or acombination thereof.

Suitable osteoinductive factors include, but are not limited to, a bonemorphogenetic protein, a growth differentiation factor, a LIMmineralization protein or a combination thereof.

Suitable analgesic agents include, but are not limited to,acetaminophen, lidocaine, bupivicaine, opioid analgesics such asbuprenorphine, butorphanol, dextromoramide, dezocine,dextropropoxyphene, diamorphine, fentanyl, alfentanil, sufentanil,hydrocodone, hydromorphone, ketobemidone, levomethadyl, mepiridine,methadone, morphine, nalbuphine, opium, oxycodone, papaveretum,pentazocine, pethidine, phenoperidine, piritramide, dextropropoxyphene,remifentanil, tilidine, tramadol, codeine, dihydrocodeine, meptazinol,dezocine, eptazocine, flupirtine or a combination thereof. Analgesicsalso include agents with analgesic properties, such as for example,amitriptyline, carbamazepine, gabapentin, pregabalin, clonidine, or acombination thereof.

A “depot” includes but is not limited to capsules, microspheres,particles, coating, matrices, wafers, pills, pellets or otherpharmaceutical delivery compositions. In various embodiments, the depotmay comprise a bioerodible, a bioabsorbable, and/or a biodegradablebiopolymer that may provide immediate release, or sustained release ofthe drug. Examples of suitable sustained release biopolymers include butare not limited to poly(alpha-hydroxy acids), poly(lactide-co-glycolide)(PLGA), polylactide (PLA), polyglycolide (PG), polyethylene glycol (PEG)conjugates of poly(alpha-hydroxy acids), poly(orthoester)s (POE),polyaspirins, polyphosphagenes, collagen, starch, pre-gelatinizedstarch, hyaluronic acid, chitosans, gelatin, alginates, albumin, fibrin,vitamin E analogs, such as alpha tocopheryl acetate, d-alpha tocopherylsuccinate, D,L-lactide, or L-lactide, -caprolactone, dextrans,vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBTcopolymer (polyactive), methacrylates, poly(N-isopropylacrylamide),PEO-PPO-PEO (pluronics), PEO-PPO-PAA copolymers, PLGA-PEO-PLGA, PEG-PLG,PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymers, SAIB (sucroseacetate isobutyrate) or combinations thereof. As persons of ordinaryskill are aware, mPEG may be used as a plasticizer for PLGA, but otherpolymers/excipients may be used to achieve the same effect. mPEG impartsmalleability to the resulting formulations. In various embodiments, thedrug depot comprises poly(lactide-co-glycolide) (PLGA), polylactide(PLA), polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide,D,L-lactide-ε-caprolactone, D,L-lactide-glycolide-ε-caprolactone or acombination thereof.

In various embodiments, the drug depot comprises drug pellets loadedwith a therapeutically effective amount of the therapeutic agent,wherein the pellets are injected into a synovial joint, a disc space, aspinal canal, or a soft tissue surrounding the spinal canal. In variousembodiments, the drug pellets comprise a gel in viscous form andmicrospheres loaded with a therapeutic agent, wherein the combination ofgel and microspheres are positioned into a synovial joint, disc space, aspinal canal, or a soft tissue surrounding the spinal canal of asubject.

A “therapeutically effective amount” is such that when administered, thedrug results in alteration of the biological activity, such as, forexample, inhibition of inflammation, reduction or alleviation of pain,improvement in the condition, etc. The dosage administered to a patientcan be as single or multiple doses depending upon a variety of factors,including the drug's pharmacokinetic properties, the route ofadministration, patient conditions and characteristics (sex, age, bodyweight, health, size, etc.), extent of symptoms, concurrent treatments,frequency of treatment and the effect desired.

In one exemplary embodiment, the drug depot is in the form of a pellet.The pellet can be any shape, such as for example, bullet shaped,spherical, substantially spherical, flaked, rod shaped, square, oval,etc. In various embodiments, an aspect ratio (a ratio of the length ofthe pellet divided by the width found at an angle of 90° in respect tothe length) which is less than about 1.4 to about 1.05. The proximal endof the drug pellet may allow the plunger tip to snuggly fit within theproximal end of the drug pellet for easier drug delivery. The distal endof the drug pellet may be rounded for easier insertion at the site.

In various embodiments, the drug pellet comprises a bullet-shaped bodythat is made from a biodegradable material. In alternative embodiments,the body of the pellet may be made from a non-biodegradable material. Anon-biodegradable body could be a porous hollow chamber filled with thetherapeutic agent alone or incorporated into a degradable polymer. Itmay be desirable to make the body non-degradable to be able to retrieveit after it has released its contents. Non-limiting examples of suitablebiodegradable materials for the pellet body include polyorthoesters(POE), polylacticglycolic acid (PLGA) polysacharides (Saber technology),polycapralactone, polyfumarate, tyrosine polycarbonate, etc.

In various embodiments, the non-biodegradable material can have amolecular weight of about 2,000 Daltons (Da) to about 3,000,000 Da. Insome embodiments, the suitable materials have a molecular weight ofabout 2,000, 5,000, 10,000, 15,000, 20,000, 25,000, 30,000, 35,000,40,000, 45,000, 50,000, 55,000, 60,000, 65,000, 70,000, 75,000, 100,000,150,000, 200,000, 250,000, 300,000, 350,000, 400,000, 450,000, 500,000,550,000, 600,000, 650,000, 700,000, 750,000, 800,000, 850,000, 900,000,950,000, 1,000,000, 1,025,000, 1,050,000, 1,100,000, 1,150,000,1,200,000, 1,250,000, 1,300,000, 1,350,000, 1,400,000, 1,450,000,1,500,000, 1,550,000, 1,600,000, 1,650,000, 1,700,000, 1,750,000,1,800,000, 1,850,000, 1,900,000, 1,950,000, 2,000,000, 2,025,000,2,050,000, 2,100,000, 2,150,000, 2,200,000, 2,250,000, 2,300,000,2,350,000, 2,400,000, 2,450,000, 2,500,000, 2,550,000, 2,600,000,2,650,000, 2,700,000, 2,750,000, 2,800,000, 2,850,000, 2,900,000,2,950,000 or 3,000,000 Da.

In various embodiments, the non-biodegradable body is porous. In someembodiments, the body is 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,65, 70, 75, 80, 85, 90, 95 or 99% porous. In various embodiments, thepores of the body have a pore size from about 2 to 350 microns. In someembodiments, the pores of the body have a pore size of about 2, 5, 10,15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100,105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170,175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240,245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310,315, 320, 325, 330, 335, 340, 345 and/or 350 microns.

In some embodiments, the body may be solid, and the therapeutic agentmay be dispersed throughout the material that forms the body. Thedispersal of the therapeutic agent may be even throughout the body.Alternatively, the concentration of the therapeutic agent may varythroughout the body. As the biodegradable material of the body degradesat the site, the therapeutic agent is released.

In some embodiments, the material that forms the body has an inherentviscosity (IV) of from about 0.10 dL/g to about 1.2 dL/g or from about0.10 dL/g to about 0.40 dL/g. Other IV ranges include but are notlimited to about 0.05 to about 0.15 dL/g, about 0.10 to about 0.20 dL/g,about 0.15 to about 0.25 dL/g, about 0.20 to about 0.30 dL/g, about 0.25to about 0.35 dL/g, about 0.30 to about 0.35 dL/g, about 0.35 to about0.45 dL/g, about 0.40 to about 0.45 dL/g, about 0.45 to about 0.55 dL/g,about 0.50 to about 0.70 dL/g, about 0.55 to about 0.6 dL/g, about 0.60to about 0.80 dL/g, about 0.70 to about 0.90 dL/g, about 0.80 to about1.00 dL/g, about 0.90 to about 1.10 dL/g, about 1.0 to about 1.2 dL/g,about 1.1 to about 1.3 dL/g, about 1.2 to about 1.4 dL/g, about 1.3 toabout 1.5 dL/g, about 1.4 to about 1.6 dL/g, about 1.5 to about 1.7dL/g, about 1.6 to about 1.8 dL/g, about 1.7 to about 1.9 dL/g, or about1.8 to about 2.1 dL/g.

Procedures for making pellets include, but are not limited to,extrusion-spheroidization, for spherical pellets where the activepharmaceutical ingredient (API) and any inactive ingredients(excipients, binders, etc.) are pre-mixed, then wetted with water, in ahigh shear mixer to form a damp mass. The damp mass is then transferredinto an extruder where it is forced through a screen or die plate, whereit forms an essentially solid, cylindrical extrudate of uniform shapeand size. The size of the opening in the screen or die dictate resultantpellet size. The extrudate is fed onto a rotating disk, which may besmooth or may contain a grid (waffled, grooved, etc.) and the extrudatebreaks into small cylinders, which in time are rounded into sphericallyshaped solids. Subsequently, the pellets are dried to the desiredresidual moisture content, typically in a fluid bed dryer. Any oversizedor undersized product is removed by sieving, and the resulting pelletshave a narrow size distribution.

In various embodiments, the API is layered on the solid core of thepellet by solution or suspension layering or powder layering techniques.In solution or suspension layering, an API and any inactive ingredients(excipients, binders, etc.) are suspended or dissolved in water or anorganic solvent. The resulting liquid is sprayed onto the outside of acore particle, which may include, for example, non-pareil sugar seed(sugar sphere), microcrystalline cellulose pellets and the like, to makethe pellet having the desired potency. Solution or suspension layeringmay be conducted using a wide variety of process techniques, forexample, by fluidized bed, Wurster bottom spray techniques, or the like.When the desired potency has been achieved, pellets are dried to thedesired residual moisture content. Any oversized or undersized productmay be removed by sieving, and the resulting pellets are narrow in sizedistribution.

Powder layering may also be used to make the drug pellets. Powderedlayering involves the application of a dry powder to the pellet corematerial. The powder may contain the drug, or may include excipientssuch as a binder, flow aid, inert filler, and the like. In the powderlayering technique a pharmaceutically acceptable liquid, which may bewater, organic solvent, with or without a binder and/or excipients, isapplied to the core material while applying the dry powder until thedesired potency is achieved. When the desired potency has been achieved,the pellets may be seal coated to improve their strength, and are thendried to the desired moisture content. Any oversized or undersizedproduct is removed by sieving, and the resulting pellets are narrow insize distribution.

In one embodiment, the pellet is made using a core of biodegradablematerial, such as, for example, polyglactin, polylactone, polylactide,etc. The core is then coated with a thin layer of the API, such as ananti-inflammatory agent, analgesic agent, etc. by solution, suspension,or powdered layering until the desired potency is achieved.

In various embodiments, the drug pellets can be different sizes, forexample, from about 1 mm to 5 mm and have a diameter of from about 0.01to about 2 mm. In some embodiments, the drug pellets are 1, 2, 3, 4and/or 5 mm in size and have a diameter of about 0.01, 0.05, 0.10, 0.15,0.20, 0.25, 0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, 0.65, 0.70, 0.75,0.80, 0.85, 0.90, 0.95, 1.0, 1.05, 1.10, 1.15, 1.20, 1.25, 1.30, 1.35,1.40, 1.45, 1.50, 1.55, 1.60, 1.65, 1.70, 1.75, 1.80, 1.85, 1.90, 1.95or about 2 mm. The layer or layers will each have a layer thickness offrom about 0.005 to 1.0 mm, such as, for example, from 0.05 to 0.75 mm.In some embodiments, the layer or layers will each have a layerthickness of about 0.005, 0.010, 0.015, 0.020, 0.025, 0.030, 0.035,0.040, 0.045, 0.050, 0.055, 0.060, 0.065, 0.070, 0.075, 0.080, 0.085,0.090, 0.095, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, 0.45, 0.50,0.55, 0.60, 0.65, 0.70, 0.75, 0.80, 0.85, 0.90, 0.95 to 1.0 mm. The drugdepot chambers are often larger than the drug depot dimensions to keepthe drug depot within the drug chamber.

Like the cannula, needle, or plunger, in various embodiments, the drugdepot (e.g., pellet, cartridge, etc.) may have dose indicator markings(e.g., numbers, lines, letters, radiographic markers, etc.) to indicatethe number of drug depots delivered. In various embodiments, radiopaquemarks are positioned on the depot at opposite ends of the depot toassist in determining the position of the depot relative to thetreatment site. For example, the radiopaque marker could be a sphericalshape or a ring around the depot.

Retaining Member

In various embodiments, the drug (e.g., drug depot) is stored in theretaining member. In some embodiments, the retaining member comprisesone or more channels, each channel capable of storing a plurality ofdrug depots (e.g., pellets). In some embodiments, the retaining membercomprises one or more channels, such as, for example, one channel, twochannels, three channels, four channels, five channels or six channels.In various embodiments, each channel is capable of storing and/orholding 6 pellets. In various embodiments, the drug depot is capable ofstoring and/or holding 1, 2, 3, 4, 5, 6, 7, 8, 9 and/or 10 or morepellets. In some embodiments, each channel is capable of storing and/orholding a single pellet. In various embodiments, the retaining member iscylindrical. In various embodiments, the retaining member is linear andis slidably receivable and is perpendicular to the housing. For example,the retaining member may be a rectangular shape and slide within thewithin the wall defined by the external surface of the body to engagewith the chamber at a position perpendicular to the body.

In some embodiments, the retaining member is monolithic with the body ofthe drug delivery device. In various embodiments, the retaining memberis a separate component from the body of the drug delivery device. Invarious embodiments, the retaining member ensures retention of the drugdepots (e.g., pellets) and prevents un-intentional pellet deployment.For example, in some embodiments, the retaining member is configured toobstruct and/or retain the drug depots (e.g., pellets) from exiting thedrug delivery device and is configured to maintain the drug depotswithin the drug delivering device. In some embodiments, when the drugdepots are disposed within the passageway of the chamber, the retainingmember acts as an obstruction, preventing the drug depots from deployingfrom the drug delivery device. In various embodiments, when the drugdepots are disposed within the first channel of the retaining member,deployment of the drug depots will not occur until the retaining memberis either pushed in a direction and the plunger moves and passes throughthe first channel or when the retaining member is rotated into aposition that allows the plunger to move and pass through the firstchannel. In some embodiments, the retaining member is automatic ormanual.

In various embodiments, the drug delivery device comprises a safingand/or an un-safing mechanism that prevents unintentional deployment ofthe drug depot (e.g., pellets). In some embodiments, the safing and/orun-safing mechanism is active or passive. In some embodiments, the drugdelivery device comprises a safing or un-safing mechanism that isautomatic or manual. In some embodiments, active safing includes movingcomponents of the drug delivery device to allow delivery of the drugdepot. For example, moving the retaining member to allow the drug depotto be dispensed from the drug delivery device. In some embodiments,passive safing includes movement of the plunger to allow delivery of thedrug depot. In various embodiments, the plunger can remove the drugdepots from the drug delivery device and/or the retaining member can becontacted and moved by the plunger to remove the drug depots from thedrug delivery device for delivery to the target tissue site.

In various embodiments, the plunger contacts by pressing the drug depotand/or the retaining member which causes automatic delivery of the drugdepot to the target tissue site.

In various embodiments, the retaining member may be made from materials,such as for example, polyurethane, polyurea, polyether(amide), PEBA,thermoplastic elastomeric olefin, copolyester, and styrenicthermoplastic elastomer, steel, aluminum, stainless steel, titanium,metal alloys with high non-ferrous metal content and a low relativeproportion of iron, carbon fiber, glass fiber, plastics, ceramics or acombination thereof. In various embodiments, the retaining member is notbiodegradable.

In some embodiments, the retaining member comprises a plurality ofchannels. The channels can be spaced an equal distance from each other.For example, the channels can be spaced 0.5 mm, or 1 mm or 5 mm, or 1 cmto about 2 cm from each other. In the embodiments of the retainingmember is not penetrable by the plunger.

In some embodiments, all or a portion of the retaining member can bemade from suitable materials including but not limited topoly(alpha-hydroxy acids), poly(lactide-co-glycolide) (PLGA),polylactide (PLA), polyglycolide (PG), polyethylene glycol (PEG)conjugates of poly(alpha-hydroxy acids), mPEG, poly(orthoester)s (POE),polyaspirins, polyphosphagenes, collagen, starch, pre-gelatinizedstarch, hyaluronic acid, chitosans, gelatin, alginates, albumin, fibrin,vitamin E analogs, such as alpha tocopheryl acetate, d-alpha tocopherylsuccinate, D,L-lactide, or L-lactide, ε-caprolactone, dextrans,vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBTcopolymer (polyactive), methacrylates, poly(N-isopropylacrylamide),PEO-PPO-PEO (pluronics), PEO-PPO-PAA copolymers, PLGA-PEO-PLGA, PEG-PLG,PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymers, SAIB (sucroseacetate isobutyrate), wax, agar, agarose, gel-vitamin or combinationsthereof. In various embodiments, the superior and/or inferior coverscomprise poly(lactide-co-glycolide) (PLGA), polylactide (PLA),polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide,D,L-lactide-ε-caprolactone, D,L-lactide-glycolide-ε-caprolactone or acombination thereof.

In various embodiments, the suitable materials can have a molecularweight of about 2,000 Daltons (Da) to about 3,000,000 Da. In someembodiments, the suitable materials have a molecular weight of about2,000, 5,000, 10,000, 15,000, 20,000, 25,000, 30,000, 35,000, 40,000,45,000, 50,000, 55,000, 60,000, 65,000, 70,000, 75,000, 100,000,150,000, 200,000, 250,000, 300,000, 350,000, 400,000, 450,000, 500,000,550,000, 600,000, 650,000, 700,000, 750,000, 800,000, 850,000, 900,000,950,000, 1,000,000, 1,025,000, 1,050,000, 1,100,000, 1,150,000,1,200,000, 1,250,000, 1,300,000, 1,350,000, 1,400,000, 1,450,000,1,500,000, 1,550,000, 1,600,000, 1,650,000, 1,700,000, 1,750,000,1,800,000, 1,850,000, 1,900,000, 1,950,000, 2,000,000, 2,025,000,2,050,000, 2,100,000, 2,150,000, 2,200,000, 2,250,000, 2,300,000,2,350,000, 2,400,000, 2,450,000, 2,500,000, 2,550,000, 2,600,000,2,650,000, 2,700,000, 2,750,000, 2,800,000, 2,850,000, 2,900,000,2,950,000 or 3,000,000 Da.

In some embodiments, the suitable materials can have has an inherentviscosity (IV) of from about 0.10 dL/g to about 1.2 dL/g or from about0.10 dL/g to about 0.40 dL/g. Other IV ranges include but are notlimited to about 0.05 to about 0.15 dL/g, about 0.10 to about 0.20 dL/g,about 0.15 to about 0.25 dL/g, about 0.20 to about 0.30 dL/g, about 0.25to about 0.35 dL/g, about 0.30 to about 0.35 dL/g, about 0.35 to about0.45 dL/g, about 0.40 to about 0.45 dL/g, about 0.45 to about 0.55 dL/g,about 0.50 to about 0.70 dL/g, about 0.55 to about 0.6 dL/g, about 0.60to about 0.80 dL/g, about 0.70 to about 0.90 dL/g, about 0.80 to about1.00 dL/g, about 0.90 to about 1.10 dL/g, about 1.0 to about 1.2 dL/g,about 1.1 to about 1.3 dL/g, about 1.2 to about 1.4 dL/g, about 1.3 toabout 1.5 dL/g, about 1.4 to about 1.6 dL/g, about 1.5 to about 1.7dL/g, about 1.6 to about 1.8 dL/g, about 1.7 to about 1.9 dL/g, or about1.8 to about 2.1 dL/g.

The drug device components (e.g., cannula or needle, plunger, retainingmember, body, engagement means, etc.) may be lightweight, disposable andsterilizable such that when the device is assembled, the weight of thedevice does not substantially increase. In various embodiments, one ormore components of the device are sterilized by radiation in a terminalsterilization step in the final packaging. Terminal sterilization of aproduct provides greater assurance of sterility than from processes suchas an aseptic process, which require individual product components to besterilized separately and the final package assembled in a sterileenvironment.

Typically, in various embodiments, gamma radiation is used in theterminal sterilization step, which involves utilizing ionizing energyfrom gamma rays that penetrates deeply in the device. Gamma rays arehighly effective in killing microorganisms, they leave no residues norhave sufficient energy to impart radioactivity to the device. Gamma rayscan be employed when the device is in the package and gammasterilization does not require high pressures or vacuum conditions,thus, package seals and other components are not stressed. In addition,gamma radiation eliminates the need for permeable packaging materials.

In various embodiments, the drug delivery device provides the advantagesof ease of manufacturing in the terminal sterilization process. If thedrug pellets are preloaded in the manufacturing process, gamma radiationmay be required at higher doses to sterilize the drug depot loaded inthe cannula or needle. This is particularly so when the cannula orneedle is made from steel or metal. Thus, to sterilize the loaded depot,the dose of gamma rays must be high enough to penetrate the metal, whichmay destroy the API in the drug depot. By providing a retaining member,for example, made of plastic, the retaining member and drug pellets inthe retaining member can be sterilized, without destroying the API andthen subsequently loaded by the manufacturer or the user (e.g., surgeon,physician, nurse, etc.). Further, loading the drug depot into theretaining member or cannula is easier. This is particularly so whendealing with multi-dose drug pellets that are relatively small (e.g., 1mm to 5 mm), the user typically cannot grasp these small pellets andload them into the device. By providing them in a retaining member, theuser does not have to substantially manipulate the individual drugpellets and the risk of contaminating the pellets particularly withsterilized pellets is reduced.

In various embodiments, electron beam (e-beam) radiation may be used tosterilize one or more components of the device. E-beam radiationcomprises a form of ionizing energy, which is generally characterized bylow penetration and high-dose rates. E-beam irradiation is similar togamma processing in that it alters various chemical and molecular bondson contact, including the reproductive cells of microorganisms. Beamsproduced for e-beam sterilization are concentrated, highly-chargedstreams of electrons generated by the acceleration and conversion ofelectricity. E-beam sterilization may be used, for example, when thedrug depot includes a gelatin capsule.

Other methods may also be used to sterilize one or more components ofthe device, including, but not limited to, gas sterilization, such as,for example, with ethylene oxide or steam sterilization.

In some embodiments, the body, drug cartridge, and/or cannula aretransparent so the user can see the position of the plunger and/or thedrug depot in the channel of the passageway and/or the retaining member.Thus, indicator markings, in this embodiment, are not needed.

In various embodiments, a kit is provided for delivering a drug pelletto a site beneath the skin of a patient, the kit comprising: asterilized drug delivery device, comprising: a body comprising aproximal end and a distal end and a chamber disposed therebetween; anupper portion disposed about the proximal end of the body; a retainingmember disposed within a wall of the body and engageable with thechamber; and a plunger configured for disposal within the upper portionand the chamber, wherein the upper portion is movable about the proximalend of the body to open the chamber such that the plunger is disposedwithin a passageway defined within the chamber, and movement of theplunger in a distal direction pushes the retaining member such that thedrug moves out of the body.

In various embodiments, a kit is provided which may include additionalparts along with the drug depot device combined together to be used toimplant the drug depot. The kit may include the drug delivery device ina first compartment. The second compartment may include the any otherinstruments needed for the implant. A third compartment may includegloves, drapes, wound dressings and other procedural supplies formaintaining sterility of the implanting process, as well as aninstruction booklet. A fourth compartment may include additionalcannulas and/or needles. Each tool may be separately packaged in aplastic pouch that is radiation sterilized. A cover of the kit mayinclude illustrations of the implanting procedure and a clear plasticcover may be placed over the compartments to maintain sterility.

In various embodiments, a method is provided for delivering a drug to atarget tissue site, the method comprising: introducing a drug deliverydevice comprising a body comprising a proximal end and a distal end anda chamber comprising a passageway disposed therebetween, an upperportion disposed about the proximal end of the body that rotates aboutthe proximal end of the body to open the chamber, and a retaining memberdisposed within a wall of the body and engageable with the chamber;attaching a needle with the distal end of the body; inserting a plungerinto the passageway, and moving the plunger in a first position to pushthe retaining member outward and moving the plunger in a second positionsuch that the drug moves through the needle and is ejected from thedelivery device and into the target tissue site.

In various embodiments, the seal between the plunger tip and the cannulaor needle can be air tight so that when the cannula or plungerpenetrates the skin, at times, fluid (e.g., blood, spinal fluid,synovial fluid, etc.) may be drawn up into the cannula or needle. Thisfluid will be expelled when the plunger is re-inserted into the cannulaor needle and the drug depot is released.

The device may be used for localized and/or targeted delivery of thedrug to a patient to treat a disease or condition such as for example,rheumatoid arthritis, osteoarthritis, sciatica, carpal tunnel syndrome,lower back pain, lower extremity pain, upper extremity pain, cancer,tissue pain, post-operative pain and pain associated with injury orrepair of cervical, thoracic, and/or lumbar vertebrae or intervertebraldiscs, rotator cuff, articular joint, TMJ, tendons, ligaments, bonemuscles, and the like.

In various embodiments, the drug depot device is used to treat pain, orother diseases or conditions of the patient. Pain includes acute painand neuropathic pain. Acute pain refers to pain experienced when tissueis being damaged or is damaged (e.g., injury, infection, etc.). Ascontrasted to acute pain, neuropathic pain serves no beneficial purpose.Neuropathic pain results when pain associated with an injury orinfection continues in an area once the injury or infection hasresolved. Sciatica provides an example of pain that can transition fromacute to neuropathic pain. Sciatica refers to pain associated with thesciatic nerve which runs from the lower part of the spinal cord (thelumbar region), down the back of the leg and to the foot. Sciaticagenerally begins with a herniated disc. The herniated disc itself leadsto local immune system activation. The herniated disc also may damagethe nerve root by pinching or compressing it, leading to additionalimmune system activation in the area.

Patients include a biological system to which a treatment can beadministered. A biological system can include, for example, anindividual cell, a set of cells (e.g., a cell culture), an organ, or atissue. Additionally, the term “patient” can refer to animals,including, without limitation, humans.

Treating or treatment of a disease refers to executing a protocol, whichmay include administering one or more drugs to a patient (human orotherwise), in an effort to alleviate signs or symptoms of the disease.Alleviation can occur prior to signs or symptoms of the diseaseappearing, as well as after their appearance. Thus, “treating” or“treatment” includes “preventing” or “prevention” of disease. Inaddition, “treating” or “treatment” does not require completealleviation of signs or symptoms, does not require a cure, andspecifically includes protocols that have only a marginal effect on thepatient.

“Localized” delivery includes, delivery where one or more drugs aredeposited within a tissue, for example, a nerve root of the nervoussystem or a region of the brain, or in close proximity (within about 10cm, or preferably within about 5 cm, for example) thereto. “Targeteddelivery system” provides delivery of one or more drugs depots in aquantity of pharmaceutical composition that can be deposited at thetarget site as needed for treatment of pain, inflammation or otherdisease or condition.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to various embodimentsdescribed herein without departing from the spirit or scope of theteachings herein. Thus, it is intended that various embodiments coverother modifications and variations of various embodiments within thescope of the present teachings.

What is claimed is:
 1. A drug delivering device for delivering a drug to a target tissue site, the drug delivery device comprising: a body comprising a proximal end and a distal end and a chamber disposed therebetween; an upper portion disposed about the proximal end of the body; a retaining member disposed within a wall of the body and engageable with the chamber; and a plunger configured for disposal within the upper portion and the chamber, wherein the upper portion is movable about the proximal end of the body to open the chamber such that the plunger is disposed within a passageway defined within the chamber, and movement of the plunger in a distal direction pushes the retaining member such that the drug moves out of the body.
 2. A drug delivery device according to claim 1, wherein (i) the upper portion is rotatable and comprises an internally threaded collet and a first tab and a second tab; (ii) a needle engages the distal end of the body; (iii) a needle engages the distal end of the body and the drug is dispensed from the needle as the plunger moves through the body or (iv) the retaining member moves in an outward direction as the plunger contacts the retaining member.
 3. A drug delivery device according to claim 2, wherein the collet rotates about a threaded portion at the proximal end of the body and the chamber comprises a third tab and a fourth tab configured for engagement with the first tab and the second tab, the first and second tab configured to guide a drug depot through the body using the plunger.
 4. A drug delivery device according to claim 2, wherein the body comprises an external first flange and the collet comprises an external second flange.
 5. A drug delivery device according to claim 4, wherein the collet is rotated in a direction, aligning the external first flange and the external second flange together such that the passageway is opened and the plunger is disposed within the passageway.
 6. A drug delivery device according to claim 2, wherein the plunger comprises a handle configured to snap into the proximal end of the body.
 7. A drug delivery device according to claim 2, wherein the wall of the body comprises an opening configured for visual inspection of the drug and the drug is in depot form.
 8. A drug delivery device according to claim 1, wherein the needle disengages from the distal end of the body after the drug is delivered to the target tissue site.
 9. A drug delivery device according to claim 1, wherein the drug delivery device does not comprise an upper portion.
 10. A drug delivery device according to claim 1, wherein the retaining member is transparent and comprises a window configured for visual inspection of the drug.
 11. A drug delivery device according to claim 10, wherein the retaining member engages with the wall of the body via snap fit engagement with press fit posts, adhesive, solvent welded, heat welded, spring loaded or magnetic engagement.
 12. A drug delivery device according to claim 7, wherein the body comprises a needle alignment indicator.
 13. A drug delivery device for delivering a drug to a target tissue site, the drug delivery device comprising: a body comprising a proximal end and a distal end and a chamber comprising a passageway disposed therebetween, and an external surface comprising a first guide and a second guide; a retaining member disposed within a wall defined by the external surface of the body and engageable with the chamber; and an internal plunger comprising a handle, and configured for disposal within the body, wherein the plunger handle is configured for slidable engagement with the first guide and the second guide and movement of the plunger handle moves the plunger through the passageway of the body and engages with the retaining member such that the drug is dispensed from the delivery device.
 14. A drug delivery device according to claim 13, wherein (i) the retaining member comprises a first channel and a second channel; (ii) a needle engages the distal end of the body; or (iii) a needle engages the distal end of the body and the drug is dispensed from the needle as the plunger moves through the body
 15. A drug delivery device according to claim 14, wherein the retaining member is rotatable relative to the body and is transparent and comprises a window configured for visual inspection of the drug, and the body comprises a wing transverse to the distal end of the body.
 16. A drug delivery device according to claim 15, wherein the retaining member is rotated in a direction such that the plunger is inserted into the first channel during movement of the handle in a distal direction.
 17. A drug delivery device according to claim 15, wherein the handle is disposed about the external surface of the body and engages the first guide and the second guide via a first inner protuberance and a second inner protuberance.
 18. A drug delivery device according to claim 15, wherein the handle comprises a first part and a second part and the first part is configured for disposal within the first guide and the second part is configured for disposal within the second guide.
 19. A drug delivery device according to claim 14, wherein the handle is disposed about the external surface of the body and engages the first guide and the second guide via a first inner protuberance and a second inner protuberance and the handle engages at least a first indent defined by the external surface of the body via a third inner protuberance, and the handle is moved about the body when squeezed, and the retaining member is transparent and comprises a window configured for visual inspection of the drug, and the retaining member is pushed in an inward direction such that the plunger is inserted into the first channel during movement of the handle in a distal direction to deliver the drug to the needle.
 20. A method of delivering a drug to a target tissue site, the method comprising: introducing a drug delivery device comprising a body comprising a proximal end and a distal end and a chamber comprising a passageway disposed therebetween, an upper portion disposed about the proximal end of the body that rotates about the proximal end of the body to open the chamber, and a retaining member disposed within a wall of the body and engageable with the chamber; attaching a needle with the distal end of the body; inserting a plunger into the passageway, and moving the plunger in a first position to push the retaining member outward and moving the plunger in a second position such that the drug moves through the needle and is ejected from the delivery device and into the target tissue site.
 21. A drug delivering device for delivering a drug to a target tissue site, the drug delivery device comprising: a body comprising a proximal end and a distal end; an upper portion disposed about the proximal end of the body; a retaining member that prevents the drug from dispensing from the drug delivery device, the retaining member being disposed within a wall of the body; and a plunger having at least a portion configured for disposal within the upper portion and the body, wherein the upper portion is movable about the proximal end of the body to open the body such that the plunger is disposed within a passageway defined within the body, and movement of the plunger in a distal direction pushes the retaining member such that the drug moves out of the body.
 22. A drug delivery device according to claim 1, wherein (i) the retaining member is monolithic or separate from the body; (ii) the drug delivery device comprises a mechanism that is passive or active to prevent unintentional dispensing of the drug; or (iii) the drug delivery device comprises a mechanism that is automatic or manual. 